MEDICAL POLICY 8.01.21

Allogeneic Hematopoietic Cell Transplantation for

Myelodysplastic Syndromes and Myeloproliferative

Neoplasms

BCBSA Ref. Policy: 8.01.21

Effective Date: May 1, 2018

Last Revised: April 3, 2018

Replaces: N/A

RELATED MEDICAL POLICIES:

7.01.50 Placental and Umbilical Cord Blood as a Source of Stem Cells

8.01.15 Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia

and Small Lymphocytic Lymphoma

8.01.22 Allogeneic Hematopoietic Cell Transplantation for Genetic Diseases

and Acquired Anemias

8.01.24 Hematopoietic Cell Transplantation for Miscellaneous Solid Tumors in

Adults

8.01.25 Hematopoietic Cell Transplantation for Autoimmune Diseases

8.01.29 Hematopoietic Cell Transplantation for Hodgkin Lymphoma

8.01.511 Hematopoietic Cell Transplantation for Solid Tumors of Childhood

8.01.520 Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia

8.01.529 Hematopoietic Cell Transplantation for Non-Hodgkin Lymphomas

8.01.530 Hematopoietic Cell Transplantation for Primary Amyloidosis

8.01.531 Hematopoietic Cell Transplantation for Waldenstrom

Macroglobulinemia

8.01.532 Hematopoietic Cell Transplantation in the Treatment of Germ-Cell

Tumors

Select a hyperlink below to be directed to that section.

POLICY CRITERIA | CODING | RELATED INFORMATION

EVIDENCE REVIEW | REFERENCES | HISTORY

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Introduction

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are diseases of

bone marrow and the blood cells they produce. These disorders can turn into a certain type of

leukemia (acute myelocytic leukemia, or AML). A type of treatment called a hematopoietic stem

cell transplant is sometimes used to treat these conditions.

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Hematopoietic stem cells are cells that are made within the bone marrow and can develop into

many different types of blood cells. In a hematopoietic stem cell transplant, stem cells can be

taken from a donor and transplanted into the person with the MDS or MPN. When the stem

cells are harvested from a donor, it is called an allogeneic hematopoietic stem cell transplant.

This policy discusses when a hematopoietic stem cell transplant may be medically necessary to

treat myelodysplastic syndromes and myeloproliferative neoplasms.

Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The

rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for

providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can

be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a

service may be covered.

Policy Coverage Criteria

Treatment Medical Necessity Myeloablative allogeneic

hematopoietic cell

transplantation

Myeloablative allogeneic hematopoietic cell transplantation

(allo-HCT) may be considered medically necessary as a

treatment of:

Myelodysplastic syndromes (MDS)

OR

Myeloproliferative neoplasms (MPN)

Reduced-intensity

conditioning allogeneic

hematopoietic cell

transplantation

Reduced-intensity conditioning allo-HCT may be considered

medically necessary as a treatment of:

Myelodysplastic syndromes

OR

Myeloproliferative neoplasms in patients who, for medical

reasons, would be unable to tolerate a myeloablative

conditioning regimen

Myeloid Neoplasms

The myeloid neoplasms are categorized according to criteria developed by the World Health

Organization (WHO). They are risk-stratified according to the International Prognostic Scoring

System (IPSS).

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2008 WHO Classification Scheme for Myeloid Neoplasms Acute myeloid leukemia (AML)

Myelodysplastic syndromes (MDS)

Myeloproliferative neoplasms (MPN)

o Chronic myelogenous leukemia

o Polycythemia vera

o Essential thrombocythemia

o Primary myelofibrosis

o Chronic neutrophilic leukemia

o Chronic eosinophilic leukemia, not otherwise categorized

o Hypereosinophilic leukemia

o Mast cell disease

o MPNs, unclassifiable

MDS/MPN

o Chronic myelomonocytic leukemia

o Juvenile myelomonocytic leukemia

o Atypical chronic myeloid leukemia

o MDS/MPN, unclassifiable

Myeloid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, or

FGFR1

o Myeloid neoplasms associate with PDGFRA rearrangement

o Myeloid neoplasms associate with PDGFRB rearrangement

o Myeloid neoplasms associate with FGFR1 rearrangement (8p11 myeloproliferative

syndrome)

2008 WHO Classification of MDS Refractory anemia (RA)

RA with ring sideroblasts (RARS)

Refractory cytopenia with multilineage dysplasia (RCMD)

RCMD with ring sideroblasts

RA with excess blasts 1 and 2 (RAEB 1 and 2)

Del 5q syndrome

Unclassified MDS

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Risk Stratification of Myelodysplastic Syndromes

Risk stratification for MDS is performed using the IPSS (see Table 1). This system was developed

after pooling data from 7 studies that used independent, risk-based prognostic factors. The

prognostic model and the scoring system were based on blast count, degree of cytopenia, and

blast percentage. Risk scores were weighted relative to their statistical power. This system is

widely used to group patients into either low -risk and high-risk groups (see Table 2). The low-

risk group includes low -risk and intermediate -1 IPSS groups; treatment goals in low-risk MDS

patients are to improve quality of life and achieve transfusion independence. In the high-risk

group, which includes intermediate -2 and high-risk IPSS groups, treatment goals are slowing

disease progression to AML and improving survival. The IPSS is usually calculated at the time of

diagnosis. The role of lactate dehydrogenase, marrow fibrosis, and 2-microglobulin also should

be considered after establishing the IPSS. If elevated, the prognostic category worsens by one

category level.

Table 1. IPSS: Myelodysplastic Syndrome Prognostic Variables

Variable 0 0.5 1.0 1.5 2.0

Marrow blasts, %

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An updated 5-category IPSS has been proposed for prognosis in patients with primary MDS or

secondary AML to account for chromosomal abnormalities frequently seen in MDS (Schanz et al,

2012). This system stratifies patients into 5 categories: very poor, poor, intermediate, good, and

very good. There has also been an investigation into using the 5-category IPSS to better

characterize risk in MDS.

Given the long natural history of MDS, allo-HCT is typically considered in patients with

increasing numbers of blasts, signaling a possible transformation to acute myeloid leukemia

(AML). Subtypes falling into this category include refractory anemia with excess blasts, refractory

anemia with excess blasts in transformation, or chronic myelomonocytic leukemia.

Patients with refractory anemia with or without ringed sideroblasts may be considered

candidates for allo-HCT when chromosomal abnormalities are present or the disorder is

associated with the development of significant cytopenias (eg, neutrophils

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Red blood cell (RBC) transfusion dependence

Neutropenia

Thrombocytopenia

High-risk cytogenetics

Increasing blast percentage

MPN

Cytopenias

Transfusion dependence

Increasing blast percentage over 5%

Age 60 to 65 years

Coding

Code Description

CPT 38232 Bone marrow harvesting for transplantation; autologous

38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor

HCPCS

S2150 Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or

autologous, harvesting, transplantation, and related complications; including: pheresis

and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization

with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative

services; and the number of days of pre and post transplant care in the global

definition

Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS

codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS).

Related Information

Page | 7 of 24

N/A

Evidence Review

Description

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) refer to a

heterogeneous group of clonal hematopoietic disorders with the potential to transform into

acute myelocytic leukemia (AML). Allogeneic hematopoietic cell transplantation (allo-HCT) has

been proposed as a curative treatment option for patients with these disorders.

Background

Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) can occur as a primary (idiopathic) disease or can be

secondary to cytotoxic therapy, ionizing radiation, or other environmental insult. Chromosomal

abnormalities are seen in 40% to 60% of patients, frequently involving deletions of chromosome

5 or 7, or an extra chromosome as in trisomy 8. Most MDS diagnoses occur in individuals older

than age 55-60 years, with an age-adjusted incidence of approximately 62% among individuals

older than age 70 years. Patients succumb either to disease progression to acute myelocytic

leukemia (AML) or to complications of pancytopenias. Patients with higher blast counts or

complex cytogenetic abnormalities have a greater likelihood of progressing to AML than do

other patients.

MDS Classification and Prognosis

The French-American-British (FAB) system has been used to classify MDS into 5 subtypes: (1)

refractory anemia (RA); (2) refractory anemia with ringed sideroblasts (RARS); (3) refractory

anemia with excess blasts (RAEB); (4) refractory anemia with excess blasts in transformation; and,

(5) chronic myelomonocytic leukemia. However, the FAB system has been supplanted by that of

the World Health Organization (WHO), which records the number of lineages in which dysplasia

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is seen (unilineage vs multilineage), separates the 5q- syndrome, and reduces the threshold

maximum blast percentage for the diagnosis of MDS from 30% to 20% (see the Policy

Coverage Criteria section for WHO classification scheme for myeloid neoplasms).

The most commonly used prognostic scoring system for MDS is the International Prognostic

Scoring System (IPSS), which groups patients into 1 of 4 prognostic categories based on the

number of cytopenias, cytogenetic profile, and the percentage of blasts in the bone marrow.

This system underweights the clinical importance of severe, life-threatening neutropenia and

thrombocytopenia in therapeutic decisions and does not account for the rate of change in

critical parameters (eg, peripheral blood counts, blast percentage). However, the IPSS has been

useful in comparative analysis of clinical trial results and its utility confirmed at many institutions.

An updated 5-category IPSS has been proposed for prognosis in patients with primary MDS or

secondary AML to account for chromosomal abnormalities frequently seen in MDS.1 This system

stratifies patients into 5 categories: very poor, poor, intermediate, good, and very good. There

has been an investigation into using the 5-category IPSS to better characterize risk in MDS. A

second prognostic scoring system incorporates the WHO subgroup classification that accounts

for blast percentage, cytogenetics, and severity of cytopenias as assessed by transfusion

requirements. The WHO Classification-based Prognostic Scoring System (WPSS) uses a 6-

category system, which allows more precise prognostication of overall survival (OS) duration, as

well as risk for progression to AML. This system, however, is not yet in widespread use in clinical

trials.

MDS Treatment

Treatment of non-progressing MDS has involved best supportive care, including red blood cell

(RBC) and platelet transfusions and antibiotics. Active therapy was given only when MDS

progressed to AML or resembled AML with severe cytopenias. An array of therapies are now

available to treat MDS, including hematopoietic growth factors (eg, erythropoietin, darbepoetin,

granulocyte colony-stimulating factor), transcriptional-modifying therapy (eg, U.S. Food and

Drug Administration [FDA]approved hypomethylating agents, nonapproved histone

deacetylase inhibitors), immunomodulators (eg, lenalidomide, thalidomide, antithymocyte

globulin, cyclosporine A), low-dose chemotherapy (eg, cytarabine), and allo-HCT. Given the

spectrum of treatments available, the goal of therapy must be decided upfront whether it is to

improve anemia, thrombocytopenia, or neutropenia, to eliminate the need for red blood cell

transfusion; to achieve complete remission, or to cure the disease.

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Allo-HCT is the only approach with curative potential, but its use is governed by patient age,

performance status, medical comorbidities, the patients risk preference, and severity of MDS at

presentation.

Chronic Myeloproliferative Neoplasms

Chronic Myeloproliferative neoplasms (MPN) are clonal bone marrow stem-cell disorders; as a

group, approximately 8400 MPN are diagnosed annually in the United States. Like MDS, MPN

primarily occur in older individuals, with approximately 67% reported in patients aged 60 years

and older.

MPN are characterized by the slow but progressive expansion of a clone of cells with the

potential may evolve into a blast crisis similar to AML. They share a common stem cell-derived

clonal heritage, with phenotypic diversity attributed to abnormal variations in signal

transduction as the result of a spectrum of mutations that affect protein tyrosine kinases or

related molecules. The unifying characteristic common to all MPNs is effective clonal

myeloproliferation resulting in peripheral granulocytosis, thrombocytosis, or erythrocytosis that

is devoid of dyserythropoiesis, granulocytic dysplasia, or monocytosis.

MPN Classification

In 2008, a new WHO classification scheme replaced the term chronic myeloproliferative disorder

with the term myeloproliferative neoplasm. MPN are a subdivision of myeloid neoplasms that

includes the 4 classic disorders: chronic myeloid leukemia (CML), polycythemia vera, essential

thrombocytopenia, and primary myelofibrosis. The WHO classification also includes chronic

neutrophilic leukemia, chronic eosinophilic leukemia/hypereosinophilic syndrome, mast cell

disease, and MPNs unclassifiable.

MPN Treatment

In indolent, nonprogressing cases, therapeutic approaches are based on relief of symptoms.

Supportive therapy may include prevention of thromboembolic events. Hydroxyurea may be

used in cases of high-risk essential thrombocytosis and polycythemia vera and intermediate-

and high-risk primary myelofibrosis.

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In 2011, the FDA approved the orally administered selective Janus kinase 1 and 2 inhibitor

ruxolitinib for the treatment of intermediate- or high-risk myelofibrosis. Ruxolitinib has been

associated with improved OS, spleen size, and symptoms of myelofibrosis when compared with

placebo.2 The COMFORT-II trial (2013) compared ruxolitinib with best available therapy in

patients with intermediate- and high-risk myelofibrosis, and demonstrated improvements in

spleen volume and OS.3 In a randomized trial comparing ruxolitinib with best available therapy

(including antineoplastic agents, most commonly hydroxyurea, glucocorticoids), with no therapy

for treatment of myelofibrosis, Harrison et al (2012) reported improvements in spleen size and

quality of life, but not OS.4

Myeloablative allo-HCT has been considered the only potentially curative therapy, but because

most patients are of advanced age with attendant comorbidities, its use is limited to those who

can tolerate often severe treatment-related adverse events of this procedure. However, the use

of RIC for allo-HCT has extended the potential benefits of this procedure to selected individuals

with these disorders.

Hematopoietic Cell Transplantation (HCT)

Hematopoietic stem cells may be obtained from the transplant recipient (autologous HCT) or

from a donor (allo-HCT). They can be harvested from bone marrow, peripheral blood, or

umbilical cord blood shortly after delivery of neonates. Although cord blood is an allogeneic

source, the stem cells in it are antigenically naive and thus are associated with a lower

incidence of rejection or graft-versus-host disease (GVHD). Cord blood is discussed in greater

detail in a separate policy (see Related Policies).

Immunologic compatibility between infused hematopoietic stem cells and the recipient is not an

issue in autologous HCT. However, immunologic compatibility between donor and patient is a

critical factor for achieving a good outcome of allo-HCT. Compatibility is established by typing

of human leukocyte antigen (HLA) using cellular, serologic, or molecular techniques. HLA refers

to the tissue type expressed at the HLA-A, -B, and -DR loci on each arm of chromosome 6.

Depending on the disease being treated, an acceptable donor will match the patient at all or

most of the HLA loci.

Conventional Preparative Conditioning for HCT

The conventional (classical) practice of allo-HCT involves administration of cytotoxic agents

(eg, cyclophosphamide, busulfan) with or without total body irradiation at doses sufficient to

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destroy endogenous hematopoietic capability in the recipient. The beneficial treatment effect in

this procedure is due to a combination of initial eradication of malignant cells and subsequent

graft-versus-malignancy (GVM) effect that develops after engraftment of allogeneic stem cells

within the patients bone marrow space. While the slower GVM effect is considered to be the

potentially curative component, it may be overwhelmed by extant disease without the use of

pre-transplant conditioning. However, intense conditioning regimens are limited to patients who

are sufficiently fit medically to tolerate substantial adverse effects. These effects include pre-

engraftment opportunistic infections secondary to loss of endogenous bone marrow function

and organ damage and failure caused by the cytotoxic drugs. Furthermore, in any allo-HCT,

immune suppressant drugs are required to minimize graft rejection and GVHD, which also

increases susceptibility of the patient to opportunistic infections.

Reduced Intensity Conditioning (RIC) for Allo-HCT

RIC refers to the pre-transplant use of lower doses or less intense regimens of cytotoxic drugs or

radiation than are used in conventional full-dose myeloablative (MA) conditioning treatments.

The goal of RIC is to reduce disease burden and to minimize as much as possible the associated

treatment-related morbidity and nonrelapse mortality (NRM) in the period during which the

beneficial graft-versus-malignancy effect of allogeneic transplantation develops. Although the

definition of RIC remains arbitrary, with numerous versions employed, all seek to balance the

competing effects of NRM and relapse due to residual disease. RIC regimens can be viewed as a

continuum in their effects, from nearly totally myeloablative to minimally myeloablative with

lymphoablation, and intensity tailored to specific diseases and patient condition. Patients who

undergo RIC with allo-HCT initially demonstrate donor cell engraftment and bone marrow

mixed chimerism. Most will subsequently convert to full-donor chimerism, which may be

supplemented with donor lymphocyte infusions to eradicate residual malignant cells. For the

purposes of this Policy, the term reduced-intensity conditioning will refer to all conditioning

regimens intended to be nonmyeloablative, as opposed to fully myeloablative (conventional)

regimens.

Summary of Evidence

For individuals who have myelodysplastic syndromes (MDS) or myeloproliferative neoplasms

(MPN) who receive myeloablative conditioning allogeneic hematopoietic cell transplantation

(allo-HCT), the evidence includes case series, which are often heterogeneous in terms of

diseases included. Relevant outcomes are overall survival, disease-specific survival, and

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treatment-related morbidity and mortality. Primarily uncontrolled, observational studies of HCT

for MDS have reported a relatively large range of overall and progression-free survival rates,

which reflect the heterogeneity in patient populations, conditioning regimens, and other factors.

Reported estimates for 3- to 5-year overall survival of 40% to 50% are typical. For HCT for MPN,

data are more limited. At least 1 comparative study of HCT for myelofibrosis has demonstrated

improved survival with HCT compared with standard therapy. At present, HCT is the only

potentially curative treatment option for patients with MDS and MPN. The evidence is sufficient

to determine that the technology results in a meaningful improvement in the net health

outcome.

For individuals who have MDS or MPN who receive reduced-intensity conditioning (RIC) allo-

HCT, the evidence includes primarily retrospective observational series. Relevant outcomes are

overall survival, disease-specific survival, and treatment-related morbidity and mortality. Direct,

prospective comparisons of outcomes after HCT with either myeloablative conditioning or RIC in

either MDS or MPN are not available. Evidence from retrospective, nonrandomized comparisons

has suggested that RIC may be used in patients who are older and have more comorbidities

without significantly worsening overall survival. RIC appears to be associated with lower rates of

nonrelapse mortality but higher cancer relapse than myeloablative HCT. At present, HCT is the

only potentially curative treatment option for patients with MDS and MPN. The evidence is

sufficient to determine that the technology results in a meaningful improvement in the net

health outcome.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 3.

Table 3. Summary of Key Trials

NCT No. Trial Name Planned

Enrollment

Completion

Date

Ongoing

NCT01366612 PRO#1278: A Phase III Study of Fludarabine and Busulfan

Versus Fludarabine, Busulfan and Low Dose Total Body

Irradiation in Patients Receiving an Allogeneic

Hematopoietic Stem Cell Transplant

54 Aug 2018

NCT00739141 Conditioning Regimen and the Transplantation of 80 Aug 2018

https://www.clinicaltrials.gov/ct2/show/NCT01366612?term=NCT01366612&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00739141?term=NCT00739141&rank=1

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NCT No. Trial Name Planned

Enrollment

Completion

Date

Unrelated Donor Umbilical Cord Blood in Patients with

Hematologic Malignancies

NCT00176930 Allogeneic Transplant for Hematological Malignancy 350 Dec 2017

NCT02581007 Reduced Intensity Conditioning and Transplantation of

Partially HLA-Mismatched Peripheral Blood Stem Cells for

Patients with Hematologic Malignancies

30 Feb 2018

NCT00887068 Randomized Controlled Study of Post-transplant

Azacitidine for Prevention of Acute Myelogenous Leukemia

and Myelodysplastic Syndrome Relapse

246 Apr 2018

NCT01471444a A Randomized Study of Once Daily Fludarabine-

Clofarabine Versus Fludarabine Alone Combined With

Intravenous Busulfan Followed by Allogeneic

Hematopoietic Stem Cell Transplantation for Acute

Myeloid Leukemia (AML) and Myelodysplastic Syndrome

(MDS)

250 Nov 2018

NCT00822393 Clinical Phase III Trial Treosulfan-Based Conditioning

Versus Reduced-Intensity Conditioning (RIC) Prior to

Allogeneic Hematopoietic Stem Cell Transplantation in

Patients with AML or MDS Considered Ineligible to

Standard Conditioning Regimens

960 Mar 2019

NCT02626715 Reduced Intensity Conditioning (RIC) and Myeloablative

Conditioning (MAC) for HCT in AML/MDS

16 Sep 2019

NCT01760655 Reduced Intensity Conditioning Before Donor Stem Cell

Transplant in Treating Patients with High-Risk Hematologic

Malignancies

50 Jan 2020

NCT02757989 Allogeneic Hematopoietic Stem Cell Transplantation in

Patients with Myelodysplastic Syndrome Low Risk

105 Apr 2021

NCT: national clinical trial. a Denotes industry-sponsored or cosponsored trial.

Clinical Input Received from Physician Specialty Societies and Academic

Medical Centers

While the various physician specialty societies and academic medical centers may collaborate

with and make recommendations during this process, through the provision of appropriate

https://www.clinicaltrials.gov/ct2/show/NCT00176930?term=NCT00176930&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02581007?term=NCT02581007&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00887068?term=NCT00887068&rank=1https://www.clinicaltrials.gov/ct2/show/NCT01471444?term=NCT01471444&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00822393?term=NCT00822393&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02626715?term=NCT02626715&rank=1https://www.clinicaltrials.gov/ct2/show/NCT01760655?term=NCT01760655&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02757989?term=NCT02757989&rank=1

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reviewers, input received does not represent an endorsement or position statement by the

physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 2 academic medical center specialists while this

policy was under review in 2009. There was consensus among reviewers that reduced-intensity

conditioning allogeneic hematopoietic cell transplantation (HCT) was of value in patients with

myelodysplastic syndromes and myeloproliferative neoplasms who would be medically unable

to tolerate a myeloablative HCT.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network Guidelines

Current National Comprehensive Cancer Network (NCCN) clinical practice guidelines for

myelodysplastic syndromes (MDS; v.1.2018) make the following recommendation about

hematopoietic cell transplantation (HCT) in general48:

For patients who are transplant candidates, the first choice of a donor has remained an HLA

[human leukocyte antigen]-matched sibling, although results with HLA-matched unrelated

donors have improved to levels comparable to those obtained with HLA-matched siblings.

With the increasing use of cord blood or HLA-haploidentical related donors, HCT has

become a viable option for many patients. High-dose conditioning is typically used for

younger patients, whereas RIC [reduced-intensity conditioning] for HCT is generally the

strategy in older individuals.

Specific NCCN guidelines related to HCT for MDS are outlined in Table 4.48

Table 4: Guidelines for Allo-HCT for Myelodysplastic Syndromes

Prognostic Category Recommendations for HCT

IPSS low/intermediate-1

OR

IPSS-R very low, low, intermediate

OR

WPSS very low, low, intermediate

Consider allo-HCT for patients who have clinically relevant

thrombocytopenia or neutropenia or increased marrow blasts, with

disease progression or no response after azacitidine/decitabine or

immunosuppressive therapy

Consider allo-HCT for patients who have symptomatic anemia with no 5q

deletion, with serum erythropoietin level >500 mU/mL, with poor

probability of response to immunosuppressive therapy, and no response

or intolerance to azacitidine/decitabine or immunosuppressive therapy

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Prognostic Category Recommendations for HCT

IPSS intermediate-2, high

OR

IPSS-R intermediate, high, very high

OR

WPSS high, very high

Recommend allo-HCT if a high-intensity therapy candidate and

transplant candidate and donor stem cell source is available

allo: allogeneic; HCT: hematopoietic cell transplantation; IPSS: International Prognostic Scoring System; WPSS: WHO

Classification-based Prognostic Scoring System.

NCCN developed new guidelines for myeloproliferative neoplasms (MPN) in 2017 (v.2.2017).49

Table 5 summarizes the NCCN recommendations (v.2.2018) on the use of allo-HCT for the

treatment of myeloproliferative neoplasms (MPN).49 The guidelines note that selection of allo-

HCT should be based on age, performance status, major comorbid conditions, psychosocial

status, patient preference, and availability of caregiver.

Table 5: Guidelines for Allo-HCT for Myeloproliferative Neoplasms

Prognostic Category Recommendations for Allo-HCT

Intermediate risk 1 myelofibrosis

IPSS=1

DIPSS-Plus=1

DIPSS=1 or 2

Consider observation or ruxolitinib if symptomatic or allo-HCT

Evaluation for allo-HCT is recommended for patients with low platelet

counts or complex cytogenetics

Intermediate risk 2 myelofibrosis

IPSS=2

DIPSS-Plus=2 or 3

DIPSS=3 or 4

High-risk myelofibrosis

IPSS>3

DIPSS-Plus=4 to 6

DIPSS=5 or 6

Consider allo-HCT immediately or bridging therapy can be used to

decrease marrow blasts to an acceptable level prior to transplant

Evaluation for allo-HCT is recommended for patients with low platelet

counts or complex cytogenetics

Disease progression to advanced

stage/AML

Induce remission with hypomethylating agents or intensive induction

chemotherapy followed by allo-HCT

allo: allogeneic; AML: acute myeloid leukemia; DIPSS: Dynamic International Prognostic Scoring System; HCT:

hematopoietic cell transplantation; IPSS: International Prognostic Scoring System

Page | 16 of 24

American Society for Blood and Marrow Transplantation

In 2015, the American Society for Blood and Marrow Transplantation (ASBMT) published

guidelines on indications for HCT, based on the recommendations of a multiple-stakeholder

task force.50 Table 6 summarizes categorizations for allo-HCT.

Table 6. Recommendations for the Use of HCT to Treat Myelodysplastic

Syndromes, Myelofibrosis, and Myeloproliferative Neoplasms

Indication Recommendation

Myelodysplastic syndromes

Low/intermediate-1 risk Standard of care, clinical evidence available (large clinical trials are not available;

however, sufficiently large cohort studies have shown efficacy with acceptable risk

of morbidity and mortality)

Intermediate-2/high risk Standard of care (well defined and generally supported by evidence in the form of

high quality clinical trials and/or observational studies)

Myelofibrosis and myeloproliferative neoplasms

Primary, low risk Standard of care (well defined and generally supported by evidence in the form of

high quality clinical trials and/or observational studies)

Primary, intermediate/high

risk

Standard of care (well defined and generally supported by evidence in the form of

high quality clinical trials and/or observational studies)

Secondary Standard of care (well defined and generally supported by evidence in the form of

high quality clinical trials and/or observational studies)

Hypereosinophilic syndromes,

refractory

Standard of care, rare indication (clinical trials and observational studies are not

feasible due to low incidence; small cohorts have shown efficacy with acceptable

risk of morbidity and mortality)

European Blood and Marrow Transplantation Group and European

LeukemiaNet

In 2015, the European Blood and Marrow Transplantation and European LeukemiaNet Group

published recommendations for the use of allo-HCT in primary myelofibrosis and for pre- and

posttransplant management and donor selection.51 Recommendations related to the selection

of patients for allo-HCT included:

Page | 17 of 24

All patients with intermediate-2 or high-risk disease according to IPSS, DIPSS [Dynamic

International Prognostic Scoring System], or DIPSS+, and age < 70 years, should be

considered potential candidates for allo-SCT [stem cell transplant].

Patients with intermediate-1-risk disease and age 2%, or adverse cytogenetics (as defined

by the DIPSS+ classification).

Patients with low-risk disease should not undergo allo-SCT. They should be monitored and

evaluated for transplantation when disease progression occurs.

Patients in blast transformation (blasts in PB or in BM [bone marrow] or both equal to or

>20%) are not good candidates for allo-SCT. They should receive debulking therapy and be

reconsidered for transplant after achieving a partial or complete remission of leukemia.

Although the use of molecular risk classification for the identification of candidates for allo-

SCT among intermediate-1- risk patients deserves further clinical validation, patients in this

risk category who are triple negative (that is, JAKV617F, CALR, and MPL negative) or ASXL1

positive, or both, should be considered for allo-SCT.

Medicare National Coverage

There is a national coverage determination for stem cell transplantation (110.23; formerly

110.81),52 portions of which are highlighted below:

B. Nationally Covered Indications

I. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

a. Treatment of leukemia, leukemia in remission, or aplastic anemia when it is reasonable

and necessary,

b. Treatment of severe combined immunodeficiency disease (SCID) and for the treatment

of Wiskott-Aldrich syndrome.

c. Treatment of Myelodysplastic Syndromes (MDS) pursuant to Coverage with Evidence

Development (CED) in the context of a Medicare-approved, prospective clinical study.

Medicare payment for these beneficiaries will be restricted to patients enrolled in an

approved clinical study.

Page | 18 of 24

d. Effective January 27, 2016, allogeneic HSCT for multiple myeloma is covered by

Medicare only for beneficiaries with Durie-Salmon Stage II or III multiple myeloma, or

International Staging System (ISS) Stage II or Stage III multiple myeloma, and

participating in an approved prospective clinical study that meets the criteria below.

There must be appropriate statistical techniques to control for selection bias and

confounding by age, duration of diagnosis, disease classification, International Myeloma

Working Group (IMWG) classification, ISS stage, comorbid conditions, type of

preparative/conditioning regimen, graft vs. host disease (GVHD) prophylaxis, donor type

and cell source.

e. Effective January 27, 2016, allogeneic HSCT for myelofibrosis (MF) is covered by

Medicare only for beneficiaries with Dynamic International Prognostic Scoring System

(DIPSSplus) intermediate-2 or High primary or secondary MF and participating in an

approved prospective clinical study. All Medicare approved studies must use appropriate

statistical techniques in the analysis to control for selection bias and potential

confounding by age, duration of diagnosis, disease classification, DIPSSplus score,

comorbid conditions, type of preparative/conditioning regimen, graft vs. host disease

(GVHD) prophylaxis, donor type and cell source.

f. Effective January 27, 2016, allogeneic HSCT for sickle cell disease (SCD) is covered by

Medicare only for beneficiaries with severe, symptomatic SCD who participate in an

approved prospective clinical study....

Regulatory Status

The U.S. Food and Drug Administration regulates human cells and tissues intended for

implantation, transplantation or infusion through the Center for Biologics Evaluation and

Research, under Code of Federal Regulation (CFR) title 21, parts 1270 and 1271. Hematopoietic

stem cells are included in these regulations.

References

1. Schanz J, Tuchler H, Sole F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS)

and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. Mar 10

2012;30(8):820-829. PMID 22331955

Page | 19 of 24

2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. Mar

1 2012;366(9):799-807. PMID 22375971

3. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3

study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. Dec 12 2013;122(25):4047-4053. PMID

24174625

4. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J

Med. Mar 01 2012;366(9):787-798. PMID 22375970

5. Kasner MT, Luger SM. Update on the therapy for myelodysplastic syndrome. Am J Hematol. Mar 2009;84(3):177-186. PMID

19195035

6. Kindwall-Keller T, Isola LM. The evolution of hematopoietic SCT in myelodysplastic syndrome. Bone Marrow Transplant. Apr

2009;43(8):597-609. PMID 19252532

7. Oliansky DM, Antin JH, Bennett JM, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the

therapy of myelodysplastic syndromes: an evidence-based review. Biol Blood Marrow Transplant. Feb 2009;15(2):137-172. PMID

19167676

8. Koenecke C, Gohring G, de Wreede LC, et al. Impact of the revised International Prognostic Scoring System, cytogenetics and

monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary

acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of

Blood and Marrow Transplantation. Haematologica. Mar 2015;100(3):400-408. PMID 25552702

9. Barrett AJ, Savani BN. Allogeneic stem cell transplantation for myelodysplastic syndrome. Semin Hematol. Jan 2008;45(1):49-59.

PMID 18179969

10. Blaise D, Vey N, Faucher C, et al. Current status of reduced-intensity-conditioning allogeneic stem cell transplantation for acute

myeloid leukemia. Haematologica. Apr 2007;92(4):533-541. PMID 17488664

11. Deschler B, de Witte T, Mertelsmann R, et al. Treatment decision-making for older patients with high-risk myelodysplastic

syndrome or acute myeloid leukemia: problems and approaches. Haematologica. Nov 2006;91(11):1513-1522. PMID 17082009

12. Huisman C, Meijer E, Petersen EJ, et al. Hematopoietic stem cell transplantation after reduced intensity conditioning in acute

myelogenous leukemia patients older than 40 years. Biol Blood Marrow Transplant. Feb 2008;14(2):181-186. PMID 18215778

13. Kroger N, Bornhauser M, Ehninger G, et al. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-

intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. Jun

2003;82(6):336-342. PMID 12728337

14. Laport GG, Sandmaier BM, Storer BE, et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell

transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow

Transplant. Feb 2008;14(2):246-255. PMID 18215785

15. Martino R, Caballero MD, Perez-Simon JA, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood

stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes.

Blood. Sep 15 2002;100(6):2243-2245. PMID 12200391

16. Mesa RA. Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders. Hematology Am

Soc Hematol Educ Program. Nov 2007:355-362. PMID 18024651

17. Tauro S, Craddock C, Peggs K, et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has

the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid

leukemia and myelodysplasia. J Clin Oncol. Dec 20 2005;23(36):9387-9393. PMID 16314618

18. Valcarcel D, Martino R. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in

myelodysplastic syndromes and acute myelogenous leukemia. Curr Opin Oncol. Nov 2007;19(6):660-666. PMID 17906468

Page | 20 of 24

19. Valcarcel D, Martino R, Caballero D, et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic

syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is

the strongest factor improving survival. J Clin Oncol. Feb 01 2008;26(4):577-584. PMID 18086801

20. Zeng W, Huang L, Meng F, et al. Reduced-intensity and myeloablative conditioning allogeneic hematopoietic stem cell

transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome: a meta-analysis and systematic review.

Int J Clin Exp Med. Jan 2014;7(11):4357-4368. PMID 25550955

21. Aoki K, Ishikawa T, Ishiyama K, et al. Allogeneic haematopoietic cell transplantation with reduced-intensity conditioning for

elderly patients with advanced myelodysplastic syndromes: a nationwide study. Br J Haematol. Feb 2015;168(3):463-466. PMID

25228239

22. Kim H, Lee JH, Joo YD, et al. A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus

fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic

syndrome. Ann Hematol. Sep 2012;91(9):1459-1469. PMID 22526363

23. Akhtari M. When to treat myelodysplastic syndromes. Oncology (Williston Park). May 2011;25(6):480-486. PMID 21717901

24. Deeg HJ, Sandmaier BM. Who is fit for allogeneic transplantation? Blood. Dec 2 2010;116(23):4762-4770. PMID 20702782

25. Giralt SA, Horowitz M, Weisdorf D, et al. Review of stem-cell transplantation for myelodysplastic syndromes in older patients in

the context of the Decision Memo for Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome

emanating from the Centers for Medicare and Medicaid Services. J Clin Oncol. Feb 10 2011;29(5):566-572. PMID 21220586

26. Deeg HJ, Bartenstein M. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: current status. Arch

Immunol Ther Exp (Warsz). Feb 2012;60(1):31-41. PMID 22143157

27. Garcia-Manero G. Myelodysplastic syndromes: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol.

Jul 2012;87(7):692-701. PMID 22696212

28. Kroger N. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood. Jun 14

2012;119(24):5632-5639. PMID 22504927

29. Basquiera AL, Pizzi S, Correas AG, et al. Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic

syndromes: a multicenter experience from Argentina. Pediatr Blood Cancer. Jan 2015;62(1):153-157. PMID 25264233

30. Boehm A, Sperr WR, Kalhs P, et al. Long-term follow-up after allogeneic stem cell transplantation in patients with

myelodysplastic syndromes or secondary acute myeloid leukemia: a single center experience. Wien Klin Wochenschr. Jan

2014;126(1-2):23-29. PMID 24249320

31. Damaj G, Mohty M, Robin M, et al. Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative

conditioning for patients with myelodysplastic syndrome: a study by the Societe Francaise de Greffe de Moelle et de Therapie

Cellulaire. Biol Blood Marrow Transplant. Sep 2014;20(9):1349-1355. PMID 24838178

32. Di Stasi A, Milton DR, Poon LM, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic

syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol

Blood Marrow Transplant. Dec 2014;20(12):1975-1981. PMID 25263628

33. Onida F, Brand R, van Biezen A, et al. Impact of the International Prognostic Scoring System cytogenetic risk groups on the

outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human

leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-

Chronic Malignancies Working Party. Haematologica. Oct 2014;99(10):1582-1590. PMID 25085359

34. Oran B, Kongtim P, Popat U, et al. Cytogenetics, donor type, and use of hypomethylating agents in myelodysplastic syndrome

with allogeneic stem cell transplantation. Biol Blood Marrow Transplant. Oct 2014;20(10):1618-1625. PMID 24953017

35. Yoshimi A, Strahm B, Baumann I, et al. Hematopoietic stem cell transplantation in children and young adults with secondary

myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia. Biol Blood Marrow Transplant. Mar

2014;20(3):425-429. PMID 24316460

Page | 21 of 24

36. Basquiera AL, Rivas MM, Remaggi G, et al. Allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic

syndrome: Experience of the Argentinean Group of Bone Marrow Transplantation (GATMO). Hematology. Apr 2016;21(3):162-

169. PMID 26147089

37. Symeonidis A, van Biezen A, de Wreede L, et al. Achievement of complete remission predicts outcome of allogeneic

haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic

Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. Jul 26

2015;171(2):239-246. PMID 26212516

38. Pohlen M, Groth C, Sauer T, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in

elderly patients (60 years). Bone Marrow Transplant. Nov 2016;51(11):1441-1448. PMID 27295269

39. Heidenreich S, Ziagkos D, de Wreede LC, et al. llogeneic stem cell transplantation for patients age >/= 70 years with

myelodysplastic syndrome: a retrospective study of the MDS Subcommittee of the Chronic Malignancies Working Party of the

EBMT. Biol Blood Marrow Transplant. Jan 2017;23(1):44-52. PMID 27720995

40. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and

treatment strategies. J Clin Oncol. Feb 10 2011;29(5):573-582. PMID 21220604

41. McLornan DP, Mead AJ, Jackson G, et al. Allogeneic stem cell transplantation for myelofibrosis in 2012. Br J Haematol. May

2012;157(4):413-425. PMID 22463701

42. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. Mar

2010;16(3):358-367. PMID 19879949

43. Gupta V, Malone AK, Hari PN, et al. Reduced-intensity hematopoietic cell transplantation for patients with primary

myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research. Biol Blood Marrow

Transplant. Jan 2014;20(1):89-97. PMID 24161923

44. Kroger N, Giorgino T, Scott BL, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of

age with primary myelofibrosis. Blood. May 21 2015;125(21):3347-3350; quiz 3364. PMID 25784679

45. Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with

myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and

Marrow Transplantation. Blood. Dec 17 2009;114(26):5264-5270. PMID 19812383

46. Gupta V, Kroger N, Aschan J, et al. A retrospective comparison of conventional intensity conditioning and reduced-intensity

conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis. Bone Marrow Transplant. Sep 2009;44(5):317-

320. PMID 19234505

47. Abelsson J, Merup M, Birgegard G, et al. The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.

Bone Marrow Transplant. Mar 2012;47(3):380-386. PMID 21552298

48. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes,

Version 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf Accessed May 2018.

49. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative

Neoplasms, Version 2.2018. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf Accessed May 2018.

50. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation:

guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. Nov

2015;21(11):1863-1869. PMID 26256941

51. Kroger NM, Deeg JH, Olavarria E, et al. Indication and management of allogeneic stem cell transplantation in primary

myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia. Nov 2015;29(11):2126-2133. PMID

26293647

52. Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Stem Cell Transplantation Formerly

110.8.1 (110.23). 2016; https://www.cms.gov/medicare-coverage-database/details/ncd-

https://www.nccn.org/professionals/physician_gls/pdf/mds.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/mpn.pdfhttps://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=366&ncdver=1&DocID=110.23&list_type=ncd&bc=gAAAAAgAAAAAAA%3d%3d&

Page | 22 of 24

details.aspx?NCDId=366&ncdver=1&DocID=110.23&list_type=ncd&bc=gAAAAAgAAAAAAA%3d%3d& Accessed May

2018.

History

Date Comments 02/01/00 Add to Therapy Section - New Policy. Policy represents revision of 7.03.10 to focus on

myelodysplasia and myelofibrosis. New policy statement on HDC for myelofibrosis.

11/12/02 Replace policy - Policy reviewed with no criteria changes.

07/13/04 Replace policy - Policy reviewed with literature; policy statement also now includes

mini-transplant. References added; cross-reference to BC.8.01.38 on mini-transplants

added.

07/12/05 Replace policy - Policy reviewed with literature search; no change in policy statement.

No further review scheduled.

02/06/06 Codes updated - No other changes.

06/02/06 Disclaimer and Scope Updates - No other changes.

10/09/07 Replace policy - Policy updated with literature review. Status changed from AR to BC.

References added. No change in policy statement.

11/12/07 Codes updated - CPT code 86817 removed as directed by RPIW.

05/13/08 Cross Reference Update - No other changes

03/10/09 Replace policy - Policy updated with literature search. Minor terminology changes to

policy statements; the intent of the policy statements remain unchanged. Additional

policy statements include Reduced intensity conditioning allogeneic SCT is considered

investigational as a treatment of myeloproliferative disorders and myelodysplastic

syndrome. References and codes added. High-Dose Chemotherapy removed from

the title and throughout the body of the policy and myeloproliferative diseases

added to the policy title.

12/08/09 Code Update - 86817 code added back to the policy.

02/09/10 Code Update - New 2010 codes added.

03/08/11 Replace policy - Policy updated with literature search, reference numbers 14-17 added.

Myeloproliferative Disorders replaced with Myeloproliferative Neoplasms in title and

text. Policy statements revised to indicate that RIC HCT, previously investigational, may

now be considered medically necessary as a treatment of myelodysplastic syndrome

and myeloproliferative neoplasms in patients who for medical reasons would be

unable to tolerate a myeloablative conditioning regimen. Reviewed and recommended

by OAP in February 2011.

https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=366&ncdver=1&DocID=110.23&list_type=ncd&bc=gAAAAAgAAAAAAA%3d%3d&

Page | 23 of 24

Date Comments 10/19/11 Related Policies updated; links refreshed.

01/06/12 Replace policy Policy updated with literature search; references 15-18 and 20 added.

Policy statements unchanged. ICD-10 codes added.

01/24/12 Code 38232 added.

02/09/12 CPT code 38204 was removed from the policy.

06/20/12 Minor update: Related Policies updated; 8.01.17 replaced 8.01.507 effective June 12,

2012.

08/01/12 Update Related Policies Titles: 8.01.17, 8.01.22, 8.01.30, 8.01.35, and 8.01.520. Removed

Related Policy 8.01.38 as it was archived.

10/01/12 Update Coding Section ICD-10 codes are now effective 10/01/2014.

01/29/13 Replace policy. Title revised with addition of the word Hematopoietic. Policy rationale

updated based on a literature review through September 2012. Reference 26 added;

others renumbered or removed. Policy statements unchanged.

09/30/13 Update Related Policies. Change title to 8.01.31.

10/18/13 Update Related Policies. Change title to 8.01.17.

01/21/14 Replace policy. Policy updated with literature search through October 8, 2013;

reference 14 added. Policy statements unchanged. CPT code 38230 removed from

policy; it does not apply.

02/27/14 Update Related Policies. Change title to 8.01.30.

03/21/14 Update Related Policies. Add 8.01.15 and delete 8.01.514.

04/18/14 Update Related Policies. Remove 8.01.20 and add 8.01.529.

06/24/14 Update Related Policies. Remove 8.01.35, 8.01.42 and 8.01.54, then add 8.01.530,

8.01.531 and 8.01.532.

12/03/14 Update Related Policies. Remove 8.01.21 and 8.01.26.

01/28/15 Annual Review. Policy updated with literature review through September 30, 2014.

References 1-3, 5-6, 26-32, and 37 added. Policy statements unchanged. Remove ICD-

9 and ICD-10 diagnosis codes; these are not utilized in policy adjudication.

02/19/15 Update Related Policies. Remove 8.01.30.

05/01/16 Annual Review, approved April 12, 2016. Policy updated with literature review through

October 27, 2015. References 1, 8, 21-22, 36-38, 43, and 48 added. Policy statements

unchanged. Update effective May 1, 2016.

09/01/16 Update Related Policies. Remove 8.01.27 as it was archived.

09/30/16 Coding Update. Remove CPT 86817 from coding section.

11/04/16 Coding update. Removed codes that are transplant benefit related.

Page | 24 of 24

Date Comments 04/01/17 Annual Review, approved March 14, 2017. Policy name changed to Allogeneic

Hematopoietic Cell Transplantation for Myelodysplastic Syndromes and

Myeloproliferative Neoplasms. Policy updated with literature review through

November 7, 2016; references 37-38 and 49-50 added. Changed hematopoietic stem

cell transplantation to hematopoietic cell transplantation per NCCN terminology

change. Policy statements unchanged.

08/01/17 Updated title of Related Policy 8.01.511.

11/10/17 Policy moved to new format, no changes to policy statement.

05/01/18 Annual Review, approved April 3, 2018. Policy updated with literature review through

November 2017; references updated. Removed investigational policy statements.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The

Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and

local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review

and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit

booklet or contact a member service representative to determine coverage for a specific medical service or supply.

CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). 2018 Premera

All Rights Reserved.

Scope: Medical policies are systematically developed guidelines that serve as a resource for Company staff when

determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to

the limits and conditions of the member benefit plan. Members and their providers should consult the member

benefit booklet or contact a customer service representative to determine whether there are any benefit limitations

applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

037338 (07-2016)

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(Chinese): Premera Blue Cross

800-722-1471 (TTY: 800-842-5357)

Oromoo (Cushite): Beeksisni kun odeeffannoo barbaachisaa qaba. Beeksisti kun sagantaa yookan karaa Premera Blue Cross tiin tajaajila keessan ilaalchisee odeeffannoo barbaachisaa qabaachuu dandaa. Guyyaawwan murteessaa taan beeksisa kana keessatti ilaalaa. Tarii kaffaltiidhaan deeggaramuuf yookan tajaajila fayyaa keessaniif guyyaa dhumaa irratti wanti raawwattan jiraachuu dandaa. Kaffaltii irraa bilisa haala taeen afaan keessaniin odeeffannoo argachuu fi deeggarsa argachuuf mirga ni qabaattu. Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii bilbilaa. Franais (French): Cet avis a d'importantes informations. Cet avis peut avoir d'importantes informations sur votre demande ou la couverture par l'intermdiaire de Premera Blue Cross. Le prsent avis peut contenir des dates cls. Vous devrez peut-tre prendre des mesures par certains dlais pour maintenir votre couverture de sant ou d'aide avec les cots. Vous avez le droit d'obtenir cette information et de laide dans votre langue aucun cot. Appelez le 800-722-1471 (TTY: 800-842-5357). Kreyl ayisyen (Creole): Avi sila a gen Enfmasyon Enptan ladann. Avi sila a kapab genyen enfmasyon enptan konsnan aplikasyon w lan oswa konsnan kouvti asirans lan atrav Premera Blue Cross. Kapab genyen dat ki enptan nan avi sila a. Ou ka gen pou pran kk aksyon avan sten dat limit pou ka kenbe kouvti asirans sante w la oswa pou yo ka ede w avk depans yo. Se dwa w pou resevwa enfmasyon sa a ak asistans nan lang ou pale a, san ou pa gen pou peye pou sa. Rele nan 800-722-1471 (TTY: 800-842-5357). Deutsche (German): Diese Benachrichtigung enthlt wichtige Informationen. Diese Benachrichtigung enthlt unter Umstnden wichtige Informationen bezglich Ihres Antrags auf Krankenversicherungsschutz durch Premera Blue Cross. Suchen Sie nach eventuellen wichtigen Terminen in dieser Benachrichtigung. Sie knnten bis zu bestimmten Stichtagen handeln mssen, um Ihren Krankenversicherungsschutz oder Hilfe mit den Kosten zu behalten. Sie haben das Recht, kostenlose Hilfe und Informationen in Ihrer Sprache zu erhalten. Rufen Sie an unter 800-722-1471 (TTY: 800-842-5357). Hmoob (Hmong): Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem ceeb. Tej zaum tsab ntawv tshaj xo no muaj cov ntsiab lus tseem ceeb txog koj daim ntawv thov kev pab los yog koj qhov kev pab cuam los ntawm Premera Blue Cross. Tej zaum muaj cov hnub tseem ceeb uas sau rau hauv daim ntawv no. Tej zaum koj kuj yuav tau ua qee yam uas peb kom koj ua tsis pub dhau cov caij nyoog uas teev tseg rau hauv daim ntawv no mas koj thiaj yuav tau txais kev pab cuam kho mob los yog kev pab them tej nqi kho mob ntawd. Koj muaj cai kom lawv muab cov ntshiab lus no uas tau muab sau ua koj hom lus pub dawb rau koj. Hu rau 800-722-1471 (TTY: 800-842-5357). Iloko (Ilocano): Daytoy a Pakdaar ket naglaon iti Napateg nga Impormasion. Daytoy a pakdaar mabalin nga adda ket naglaon iti napateg nga impormasion maipanggep iti apliksayonyo wenno coverage babaen iti Premera Blue Cross. Daytoy ket mabalin dagiti importante a petsa iti daytoy a pakdaar. Mabalin nga adda rumbeng nga aramidenyo nga addang sakbay dagiti partikular a naituding nga aldaw tapno mapagtalinaedyo ti coverage ti salun-atyo wenno tulong kadagiti gastos. Adda karbenganyo a mangala iti daytoy nga impormasion ken tulong iti bukodyo a pagsasao nga awan ti bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY: 800-842-5357). Italiano (Italian): Questo avviso contiene informazioni importanti. Questo avviso pu contenere informazioni importanti sulla tua domanda o copertura attraverso Premera Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe essere necessario un tuo intervento entro una scadenza determinata per consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di ottenere queste informazioni e assistenza nella tua lingua gratuitamente. Chiama 800-722-1471 (TTY: 800-842-5357).

(Japanese): Premera Blue Cross

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Premera Blue Cross

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Polskie (Polish): To ogoszenie moe zawiera wane informacje. To ogoszenie moe zawiera wane informacje odnonie Pastwa wniosku lub zakresu wiadcze poprzez Premera Blue Cross. Prosimy zwrcic uwag na kluczowe daty, ktre mog by zawarte w tym ogoszeniu aby nie przekroczy terminw w przypadku utrzymania polisy ubezpieczeniowej lub pomocy zwizanej z kosztami. Macie Pastwo prawo do bezpatnej informacji we wasnym jzyku. Zadzwocie pod 800-722-1471 (TTY: 800-842-5357). Portugus (Portuguese): Este aviso contm informaes importantes. Este aviso poder conter informaes importantes a respeito de sua aplicao ou cobertura por meio do Premera Blue Cross. Podero existir datas importantes neste aviso. Talvez seja necessrio que voc tome providncias dentro de determinados prazos para manter sua cobertura de sade ou ajuda de custos. Voc tem o direito de obter esta informao e ajuda em seu idioma e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357).

Romn (Romanian): Prezenta notificare conine informaii importante. Aceast notificare poate conine informaii importante privind cererea sau acoperirea asigurrii dumneavoastre de sntate prin Premera Blue Cross. Pot exista date cheie n aceast notificare. Este posibil s fie nevoie s acionai pn la anumite termene limit pentru a v menine acoperirea asigurrii de sntate sau asistena privitoare la costuri. Avei dreptul de a obine gratuit aceste informaii i ajutor n limba dumneavoastr. Sunai la 800-722-1471 (TTY: 800-842-5357). P (Russian): . Premera Blue Cross. . , , . . 800-722-1471 (TTY: 800-842-5357). Faasamoa (Samoan): Atonu ua iai i lenei faasilasilaga ni faamatalaga e sili ona taua e tatau ona e malamalama i ai. O lenei faasilasilaga o se fesoasoani e faamatala atili i ai i le tulaga o le polokalame, Premera Blue Cross, ua e tau fia maua atu i ai. Faamolemole, ia e iloilo faalelei i aso faapitoa oloo iai i lenei faasilasilaga taua. Masalo o lea iai ni feau e tatau ona e faia ao lei aulia le aso ua taua i lenei faasilasilaga ina ia e iai pea ma maua fesoasoani mai ai i le polokalame a le Malo oloo e iai i ai. Oloo iai iate oe le aia tatau e maua atu i lenei faasilasilaga ma lenei famatalaga i legagana e te malamalama i ai aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471 (TTY: 800-842-5357). Espaol (Spanish): Este Aviso contiene informacin importante. Es posible que este aviso contenga informacin importante acerca de su solicitud o cobertura a travs de Premera Blue Cross. Es posible que haya fechas clave en este aviso. Es posible que deba tomar alguna medida antes de determinadas fechas para mantener su cobertura mdica o ayuda con los costos. Usted tiene derecho a recibir esta informacin y ayuda en su idioma sin costo alguno. Llame al 800-722-1471 (TTY: 800-842-5357). Tagalog (Tagalog): Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na walang gastos. May karapatan ka na makakuha ng ganitong impormasyon at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471 (TTY: 800-842-5357). (Thai): Premera Blue Cross 800-722-1471 (TTY: 800-842-5357) (Ukrainian): . Premera Blue Cross. , . , , . . 800-722-1471 (TTY: 800-842-5357). Ting Vit (Vietnamese): Thng bo ny cung cp thng tin quan trng. Thng bo ny c thng tin quan trng v n xin tham gia hoc hp ng bo him ca qu v qua chng trnh Premera Blue Cross. Xin xem ngy quan trng trong thng bo ny. Qu v c th phi thc hin theo thng bo ng trong thi hn duy tr bo him sc khe hoc c tr gip thm v chi ph. Qu v c quyn c bit thng tin ny v c tr gip bng ngn ng ca mnh min ph. Xin gi s 800-722-1471 (TTY: 800-842-5357).